Resources and methods to rapidly evaluate the clinical utility of promising biomarker of risk and disease are critically needed. Preliminary assessment of promising serologic and genetic markers may be performed using available specimen banks. The proposed study will use an existing community-based cohort under follow-up for cancer outcomes. Participants donated blood specimens in 1974 (CLUE I) and 1989 (CLUE II). Serum/plasma, red blood cells and buffy coats have been stored at -70 degrees Centigrade 1989. As a member of the Early Detection Network we propose to set aside alliquots serum/plasma, red blood cells and DNA from existing cohort resources (over 58,000 specimens) as a network resource. We will expand the resource by collecting tissue specimens from Cohort participants who develop cancer. We propose to conduct another blood collection campaign in the year 2001. To obtain 40,000 blood specimens, encouraging previous CLUE participants to donate again. This will provide specimens on individuals from multiple time points and expand the cohort resources. To demonstrate the ability to rapidly and efficient evaluate multiple types of biomarkers for the early detection of cancer or markers of developing cancer we propose to study three promising biomarkers: Fatty acid synthase concentrations (FAS), a potent8ial marker for the early detection of aggressive forms of breast cancer; genetic polymorphisms in the XPD gene, a potential marker of susceptibility to the development of a second primary cancer among individuals with non-melanoma skin cancer; and tobacco-specific nitrosamine hemoglobin adducts (TSNA), a potential marker of risk for the development of lung cancer among smokers. The CLUE study cohorts will provide a mechanism to rapidly assess potential markers and aid in their transition from the laboratory to the clinical setting. The long-term characterization of the cohort and having multiple specimens are valuable for determining the validity (sensitivity and specificity) of biomarkers, changes in biomarkers over time, association with early vs late stages of carcinogenesis and assessing latency periods.